Original Article

Immunomodulatory Effects of Calcitriol through DNA Methylation Alteration of FOXP3 in the CD4+ T Cells of Mice


Vitamin D plays a variety of physiological functions, such as regulating mineral homeostasis. More recently, it has emerged as an immunomodulator player, affecting several types of immune cells, such as regulatory T (Treg) cells. It has been reported that vitamin D exerts some mediatory effects through an epigenetic mechanism. In this study, the impacts of calcitriol, the active form of vitamin D, on the methylation of the conserved non-coding sequence 2 (CNS2) region of the forkhead box P3 (Foxp3) gene promoter, were evaluated.
Fourteen C57BL/6 mice were recruited in this study and divided into two intervention and control groups. The CD4+ T cells were isolated from mice splenocytes. The expression of Foxp3, IL-10, and transforming growth factor-beta (TGF-β1) genes were relatively quantified by real-time PCR technique, and the DNA methylation percentage of every CpG site in the CNS2 region was measured individually by bisulfite-sequencing PCR.
Vitamin D Intervention significantly (p<0.05) could increase the expression of Foxp3, IL-10, and TGF-β1 gene in the CD4+ T cells of mice comparing with the control group. Meanwhile, methylation of the CNS2 region of Foxp3 promoter was significantly decreased in three of ten CpG sites in the vitamin D group compared to the control group.
The results of this study showed that vitamin D can engage the methylation process to induce Foxp3 gene expression and probably Treg cytokines profile. Further researches are needed to discover the precise epigenetic mechanisms by which vitamin D modulates the immune system.

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IssueVol 19 No 5 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v19i5.4466
Calcitriol FOXP3 gene Methylation Regulatory T-lymphocytes Vitamin D

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How to Cite
Oraei M, Bitarafan S, Mesbah-Namin SA, Noori-Zadeh A, Mansouri F, Parastouei K, Anissian A, Yekaninejad MS, Hajizadeh M, Saboor-Yaraghi AA. Immunomodulatory Effects of Calcitriol through DNA Methylation Alteration of FOXP3 in the CD4+ T Cells of Mice. Iran J Allergy Asthma Immunol. 2020;19(5):509-516.